• John W Devlin, Frederick Sieber, Oluwaseun Akeju, Babar A Khan, MacLullichAlasdair M JAMJEdinburgh Delirium Research Group, Ageing and Health, Usher Institute, University of Edinburgh, Edinburgh, United Kingdom., Edward R Marcantonio, Esther S Oh, Meera R Agar, Thiago J Avelino-Silva, Miles Berger, Lisa Burry, Elizabeth A Colantuoni, Lis A Evered, Timothy D Girard, Jin H Han, Annmarie Hosie, Christopher Hughes, Richard N Jones, Pratik P Pandharipande, Balachundhar Subramanian, Thomas G Travison, Mark van den Boogaard, Sharon K Inouye, and Network for Investigation of Delirium: Unifying Scientists (NIDUS) Writing Group.
• Department of Pharmacy and Health Systems Sciences, Bouve College of Health Sciences, Northeastern University, Boston, MA.
• Crit. Care Med. 2025 Jan 1; 53 (1): e15e28e15-e28.

ObjectivesTo summarize the delirium treatment trial literature, identify the unique challenges in delirium treatment trials, and formulate recommendations to address each in older adults.DesignA 39-member interprofessional and international expert working group of clinicians (physicians, nurses, and pharmacists) and nonclinicians (biostatisticians, epidemiologists, and trial methodologists) was convened. Four expert panels were assembled to explore key subtopics (pharmacological/nonpharmacologic treatment, methodological challenges, and novel research designs).MethodsTo provide background and context, a review of delirium treatment randomized controlled trials (RCTs) published between 2003 and 2023 was conducted and evidence gaps were identified. The four panels addressed the identified subtopics. For each subtopic, research challenges were identified and recommendations to address each were proposed through virtual discussion before a live, full-day, and in-person conference. General agreement was reached for each proposed recommendation across the entire working group via moderated conference discussion. Recommendations were synthesized across panels and iteratively discussed through rounds of virtual meetings and draft reviews.ResultsWe identified key evidence gaps through a systematic literature review, yielding 43 RCTs of delirium treatments. From this review, eight unique challenges for delirium treatment trials were identified, and recommendations to address each were made based on panel input. The recommendations start with design of interventions that consider the multifactorial nature of delirium, include both pharmacological and nonpharmacologic approaches, and target pathophysiologic pathways where possible. Selecting appropriate at-risk patients with moderate vulnerability to delirium may maximize effectiveness. Targeting patients with at least moderate delirium severity and duration will include those most likely to experience adverse outcomes. Delirium severity should be the primary outcome of choice; measurement of short- and long-term clinical outcomes will maximize clinical relevance. Finally, plans for handling informative censoring and missing data are key.ConclusionsBy addressing key delirium treatment challenges and research gaps, our recommendations may serve as a roadmap for advancing delirium treatment research in older adults.Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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